Cannabis-linked psychosis shows distinct brain patterns and higher relapse risk

Cannabis use is a known risk factor for psychosis, but it remains unclear whether cannabis-associated psychosis (CAP) differs meaningfully from non-cannabis-associated psychosis (NCAP) in clinical presentation, biology, or illness course. The objective of this study was to characterize the presentation and course of first-episode psychosis with and without cannabis exposure. In this prospective study, males hospitalized for new-onset psychosis with confirmed cannabis exposure (CAP; N=66) were compared with those without cannabis exposure (NCAP; N=53). Participants were assessed at admission and after 4 weeks of standardized inpatient treatment, using cognitive tests (CogState Schizophrenia Battery, Hopkins Verbal Learning Test), electroencephalography (EEG), and symptom scales (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Rating Scale [CDRS], Young Mania Rating Scale [YMRS]). Cognitive test performance significantly improved in the CAP group but not in the NCAP group, despite the absence of group differences at the time of admission. At admission, relative to the NCAP group, the CAP group had significantly higher power spectral density exponent in the EEG, a proxy index of cortical excitatory/inhibitory (E/I) balance. CAP participants presented with lower PANSS negative and total scores but greater depressive (CDRS) and manic (YMRS) symptoms at admission. Psychosis symptoms improved with treatment in both groups, but the CAP group experienced greater improvement in mood symptoms. Follow-up data were available for 16 CAP participants; 10 were rehospitalized for psychosis exacerbation after resuming cannabis use, whereas relapse was rare among those who remained abstinent. Relative to the NCAP group, the CAP group exhibited better cognitive function, lower cortical E/I balance, lesser negative symptoms, and greater mood symptoms. Cannabis resumption was associated with relapse, highlighting its role in illness recurrence. Together, these results raise the possibility that cannabis-associated psychosis is a distinct subtype of first-episode psychosis. Given the increasing rates of psychosis related to cannabis, further studies are needed to examine its long-term trajectory and refine treatment approaches.